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Destroying pathogen-tumor symbionts synergizing with catalytic therapy of colorectal cancer by biomimetic protein-supported single-atom nanozyme

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3837-3848页

作者： Xinyue Wang Qian Chen Yefei Zhu Kairuo Wang Yongliang Chang Xiawei Wu Weichao Bao Tongcheng Cao Hangrong Chen Yang Zhang huanlong qin Nanomedicine and Intestinal Microecology Research Center Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200072PR China State Key Laboratory of High Performance Ceramics and Superfine Microstructure Shanghai Institute of CeramicsShanghai 200050China Shanghai Key Lab of Chemical Assessment and Sustainability School of Chemical Science and EngineeringTongji University1239 Siping RoadShanghai 200092China Precision Medicine Center Taizhou Central Hospital999 Donghai RoadTaizhou 318000 ZhejiangChina

The crucial role of intratumoral bacteria in the progression of cancer has been gradually recognized with the development of sequencing *** intratumoral bacteria which have been identified as pathogens of cancer that induce progression,metastasis,and poor outcome of cancer,while tumor vascular networks and immunosuppressive microenvironment provide shelters for pathogens ***,the mutually-beneficial interplay between pathogens and tumors,named“pathogentumor symbionts”,is probably a potential therapeutic site for tumor ***,we proposed a destroying pathogen-tumor symbionts strategy that kills intratumoral pathogens,***,to break the symbiont and synergize to kill colorectal cancer(CRC)*** strategy was achieved by a groundbreaking protein-supported copper single-atom nanozyme(BSA-Cu SAN)which was inspired by the structures of native enzymes that are based on protein,with metal elements as the active ***-Cu SAN can exert catalytic therapy by generating reactive oxygen species(ROS)and depleting *** in vitro and in vivo experiments demonstrate that BSA-Cu SAN passively targets tumor sites and efficiently scavenges *** in situ to destroy pathogentumor *** a result,ROS resistance of CRC through elevated autophagy mediated by *** was relieved,contributing to apoptosis of cancer cells induced by intracellular redox imbalance generated by BSA-Cu ***,BSA-Cu SAN experiences renal clearance,avoiding long-term systemic *** work provides a feasible paradigm for destroying pathogen-tumor symbionts to block intratumoral pathogens interplay with CRC for antitumor therapy and an optimized trail for the SAN catalytic therapy by the clearable protein-supported SAN.

关键词： colorectal elevated catalytic

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Ketogenic diet alleviates colitis by reduction of colonic group 3 innate lymphoid cells through altering gut microbiome

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Signal Transduction and Targeted Therapy 2021年第5期6卷 1573-1584页

作者： Cheng Kong Xuebing Yan Yongqiang Liu Linsheng Huang Yefei Zhu Jide He Renyuan Gao Matthew F.Kalady Ajay Goel huanlong qin Yanlei Ma Department of Gastrointestinal Surgery Shanghai Tenth People's HospitalTongji UniversityShanghaiChina Research Institute of Intestinal Diseases Tongji University School of MedicineShanghaiChina Department of Cancer Biology Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Oncology Affiliated Hospital of Yangzhou UniversityYangzhou UniversityYangzhouChina sDepartment of Coloreaal Surgery Digestive Disease and Surgery InstituteCleveland ClinicClevelandOHUSA Department of Molecular Diagnostics and Experimental Therapeutics Beckman Research Institute of City of Hope Comprehensive Cancer CenterDuarteCAUSA Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina Department of Colorectal Surgery Fudan University Shanghai Cancer CenterShanghaiChina

Accumulating evidence suggests that ketogenic diets(KDs)mediate the rise of circulating ketone bodies and exert a potential antiinflammatory effect;however,the consequences of this unique diet on colitis remain *** performed a series of systematic studies using a dextran sulfate sodium(DSS)animal model of inflammatory *** were fed with a KD,low-carbohydrate diet(LCD),or normal diet(ND).Germ-free mice were utilized in validation *** tissues were analyzed by transcriptome sequencing,RT2 profiler PCR array,histopathology,and *** samples were analyzed by metabolic assay *** samples were analyzed by 16S rRNA gene sequencing,liquid chromatography-mass spectrometry and gas chromatography-mass *** observed that KD alleviated colitis by altering the gut microbiota and metabolites in a manner distinct from *** diet experiments confirmed the unique impact of KD relative to LCD with a reproducible increase in Akkermansia,whereas the opposite was observed for Escherichia/*** colitis induction,the KD protected intestinal barrier function,and reduced the production of R0Ryt+CD3_group 3 innate lymphoid cells(ILC3s)and related inflammatory cytokines(IL-17a,IL-18,IL-22,Ccl4).Finally,fecal microbiota transplantation into germ-free mice revealed that the KD-mediated colitis inhibition and ILC3 regulation were dependent on the modification of gut *** together,our study presents a global view of microbiome-metabolomics changes that occur during KD colitis treatment,and identifies the regulation of gut microbiome and ILC3s as novel targets involving in IBD dietary therapy.

关键词： colitis lymphoid consequences

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加强肠道屏障功能的认识及研究

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上海医学 2006年第8期29卷 517-521页

作者：秦环龙上海交通大学附属第六人民医院外科 200233

长期来人们对肠道功能的认识偏重于营养物的消化、吸收，肠功能监测指标和治疗也主要局限于消化、吸收营养和补充营养的肠外营养（PN）方面。对肠功能全面的概念和研究均未得到应有的重视。近十余年，随着临床医学的发展和对PN弊端的认... 详细信息

长期来人们对肠道功能的认识偏重于营养物的消化、吸收，肠功能监测指标和治疗也主要局限于消化、吸收营养和补充营养的肠外营养（PN）方面。对肠功能全面的概念和研究均未得到应有的重视。近十余年，随着临床医学的发展和对PN弊端的认识，发现肠道屏障功能障碍（barrier function dysfunction）是导致肠内细菌及毒素易位、全身炎症反应综合征（SIRS）、多器官功能障碍综合征（MODS）和多系统器官衰竭（MSOF）的一个重要因素[川。因此，肠道屏障功能已成为判断危重患者预后的一个重要指标，亦有人称肠道为“机体应激时器官功能障碍的中心”。但是其发生机制、诊断、预防和治疗仍有许多不明之处，尚有待深入研究予以阐明。

关键词：肠道屏障功能障碍全身炎症反应综合征(SIRS) 多器官功能障碍综合征多系统器官衰竭肠道功能监测指标肠外营养临床医学肠内细菌

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Fecal microbiota transplantation in clinical practice:Present controversies and future prospects

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hLife 2024年第6期2卷 269-283页

作者： Hongliang Tian Xinjun Wang Zhixun Fang Long Li Chunyan Wu Dexi Bi Ning Li Qiyi Chen huanlong qin Department of Colorectal Disease Tenth People’s Hospital of Tongji UniversityShanghaiChina Shanghai Institution of Gut Microbiota Research and Engineering Development Tenth People’s Hospital of Tongji UniversityShanghaiChina Clinical Research Center for Digestive Diseases Tongji UniversityShanghaiChina Bengbu First People’s Hospital AnhuiChina Research Institute of Intestinal Diseases Tongji University School of MedicineShanghaiChina Department of Pathology Tenth People’s Hospital of Tongji UniversityShanghaiChina Realbio Genomics Institute ShanghaiChina

The gut microbiota,serving as the only“organ”that humans can share,has been extensively applied in the treatment of various intestinal and extraintestinal diseases through fecal microbiota transplantation(FMT)*** optimizing the donor selection strategy,FMT exhibited the highest effectiveness(more than 90%)in treating acute intestinal inflammations,such as recurrent Clostridium difficile ***,the efficacy diminishes when addressing intestinal functional diseases(more than 60%),chronic intestinal inflammations or organic diseases(less than 60%),and extraintestinal diseases,particularly those lacking any gastrointestinal symptoms(less than 50%).Ongoing efforts to enhance the therapeutic response of FMT across diverse diseases represent a central focus of current clinical *** review concentrates on donor selection,recipient management,precise donor-recipient matching,antagonistic mechanism of native bacteria to transplanted bacteria,and targeted treatment strategies for different diseases,with the aim of providing practical strategies to improve the clinical efficacy of FMT.

关键词： fecal microbiota transplantation clinical research colonization antagonism

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低热量肠外营养联合生长激素在外科危重病人中的应用

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中国实用外科杂志 2000年第10期20卷 615-617页

作者：秦环龙上海市第六人民医院外科 200233

目的　探讨外科危重病人给予低热量肠外营养 (PN)支持和生长激素 (rhGH)治疗的效果。方法　对15例外科危重病人以低热量、低糖、低脂肪为总原则实施PN ,总热量不超过 6 2 8～ 83 7kJ(15～ 2 0kcal) / (kg·d) ,供氮量不超过 0 10～ 0 ... 详细信息

目的　探讨外科危重病人给予低热量肠外营养 (PN)支持和生长激素 (rhGH)治疗的效果。方法　对15例外科危重病人以低热量、低糖、低脂肪为总原则实施PN ,总热量不超过 6 2 8～ 83 7kJ(15～ 2 0kcal) / (kg·d) ,供氮量不超过 0 10～ 0 12 g/ (kg·d) ,脂肪供热不超过 40 % ,配合短程小剂量rhHG治疗。观察治疗前后血清白蛋白、前白蛋白、转铁蛋白、肌酐指数、总淋巴细胞计数和氮平衡等的变化。结果　治愈 12例 ,死亡 3例。治疗过程中未出现明显的糖、脂代谢异常和肝酶谱变化的代谢性并发症。采用低热量PN和生长激素治疗后血浆蛋白水平显著升高 ,氮平衡、肌酐指数得到明显改善。结论　低热量PN与rhGH联合应用 ,能够有效克服重症病人所出现的营养代谢障碍。

关键词：外科危重病人低热量肠外营养生长激素 PN

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外科危重病人营养支持方法的改进和疗效观察

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上海医学 2000年第12期23卷 717-720页

作者：秦环龙上海市第六人民医院外科 200233

目的　分析外科危重病人经不同热、氮需要量和不同途径营养支持治疗的效果。方法　依据危重病人的代谢特点实施肠外营养 (PN) ,对 2 2例外科危重病人早期以低热量、低氮量、低脂肪为原则 ,总热量不超过 2 0kcal·kg-1·d-1,供氮量不超过... 详细信息

目的　分析外科危重病人经不同热、氮需要量和不同途径营养支持治疗的效果。方法　依据危重病人的代谢特点实施肠外营养 (PN) ,对 2 2例外科危重病人早期以低热量、低氮量、低脂肪为原则 ,总热量不超过 2 0kcal·kg-1·d-1,供氮量不超过 0 .15g·kg-1·d-1,脂肪供热不超过 40 %为宜 ;应激消退期 ,相应增加供热、氮量 ,总热量不超过 2 5kcal·kg-1·d-1,供氮量为 0 .2 0g·kg-1·d-1,以满足机体合成代谢的需要。一旦肠道功能恢复 ,应及时过渡到肠内营养。结果　本组治愈 17例 ,死亡 5例。治疗过程中未出现明显的糖、脂代谢异常和肝酶谱变化的代谢性并发症。EN期间无严重腹泻、腹胀等并发症。结论　营养支持对危重病人至关重要。早期因病情危重 ,消化道功能差 ,以循序渐进、阶段性的肠外营养为主 ;后期以肠内营养为主 ,以减少肠道细菌和内毒素易位 ,减少肠源性感染发生率。

关键词：外科危重病人肠外营养肠内营养

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Radical resection of gastric carcinoma with pancreas and spleen preservation and functional cleaning of lymph nodes

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Chinese Medical Journal 2002年第5期115卷 736-739,154页

作者：秦环龙林超鸿上海市第六人民医院外科上海200233

OBJECTIVE: To study the clinical value of radical resection of gastric carcinoma with pancreas and spleen preservation (PSP) and functional cleaning of lymph nodes (LNs) of the spleen hillus and along the splenic artery. METHODS: Pancreas and spleen involvement was retrospectively reviewed among 439 cases of resectable carcinoma of the gastric cardia, gastric corpus and total stomach. During gastric surgery, 2 ml of methylene blue was injected into the subserosal space of the gastric cardia or corpus to observe the spread of lymphatic flow in 54 cases of gastric carcinoma. The metastatic rate of LNs in splenic hillus and along the trunk of the splenic artery (No10, No11), postoperative complications and survival rates were investigated in 63 gastric carcinoma patients that had received gastrectomy with pancreas and spleen preservation (PSP). These were compared with the pancreas preservation (PP) group and pancreas and spleen combined resection (PSR) group. RESULTS: Among these 439 cases, only 25 cases were observed with direct invasion to the pancreas (5.7%), and 10 cases with direct invasion to the spleen (2.3%). After pathological examination of the pancreatic body and tail, we found 22 cases with pancreas and spleen combined resection, 4 cases (18.2%, 4/22) with direct invasion of the capsule and 2 with invasion to the superficial parenchyma (9.1%, 2/22), without metastasis to the lymph nodes within the pancreas and spleen. The metastatic rate of No10, No11 lymph nodes were 17.5% (11/63) and 19.1% (12/63) in the PSP group, 20.8% (45/216) and 25% (54/216) in the PP group, and 20% (6/30) and 23.3% (7/30) in the PSR group. There were no statistically significant differences (P > 0.05). Injection of methylene blue into the subserosal space of the stomach did not diffuse into the spleen or pancreatic parenchyma. Postoperative complications, diabetes and mortality in PSP (0%, 0%, 0%) were lower than in PP (4.2%, 0.9%, 0.9%) or PSR (40%, 10%, 3.3%). The 5-year survival

关键词： Adult Aged Female Humans Lymph Nodes Lymphatic Metastasis Lymphatic System Male Methylene Blue Middle Aged Neoplasm Staging Pancreatic Neoplasms Postoperative Complications Splenic Neoplasms Stomach Neoplasms Survival Rate Treatment Outcome

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Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer

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Signal Transduction and Targeted Therapy 2021年第12期6卷 3730-3739页

作者： Yaohui Gao Dexi Bi Ruting Xie Man Li Jing Guo Hu Liu Xianling Guo Juemin Fang Tingting Ding Huiyuan Zhu Yuan Cao Meichun Xing Jiayi Zheng qing Xu Qian Xu qing Wei huanlong qin Department of Pathology Shanghai Tenth People’s Hospital Affiliated to Tongji University200072 ShanghaiChina Department of Oncology Shanghai Tenth People’s Hospital Affiliated to Tongji University200072 ShanghaiChina Department of Gastrointestinal Surgery Shanghai Tenth People’s Hospital Affiliated to Tongji University200072 ShanghaiChina

Given that only a subset of patients with colorectal cancer(CRC)benefit from immune checkpoint therapy,efforts are ongoing to identify markers that predict immunotherapeutic *** evidence suggests that microbes influence the efficacy of cancer *** nucleatum induces different immune responses in CRC with different microsatellite-instability(MSI)***,we investigated the effect of *** on anti-PD-L1 therapy in *** found that high *** levels correlate with improved therapeutic responses to PD-1 blockade in patients with ***,*** enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged *** *** supplementation with immunotherapy rescued the therapeutic effects of PD-L1 ***,*** induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma(IFN-γ)^(+)CD8^(+)tumor-infiltrating lymphocytes(TILs)during treatment with PD-L1 blockade,thereby augmenting tumor sensitivity to PD-L1 ***,patient-derived organoid models demonstrated that increased *** levels correlated with an improved therapeutic response to PD-L1 *** findings suggest that *** may modulate immune checkpoint therapy for CRC.

关键词： colorectal cancer interferon

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固有淋巴细胞在肠道稳态和疾病中的研究进展

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中华微生物学和免疫学杂志 2018年第6期38卷 464-467页

作者：潘登登秦环龙安徽医科大学上海临床学院上海200072 上海市第十人民医院胃肠外科 200072

固有淋巴细胞（innate lymphoid cells，ILCs）是最新发现的一类淋巴细胞家族。属于淋巴系统的固有免疫细胞。因缺乏模式识别受体和重组受体而不能直接参与特异性免疫应答。根据表达的转录因子和分泌的细胞因子不同可将ILCs分为ILC1、I... 详细信息

固有淋巴细胞（innate lymphoid cells，ILCs）是最新发现的一类淋巴细胞家族。属于淋巴系统的固有免疫细胞。因缺乏模式识别受体和重组受体而不能直接参与特异性免疫应答。根据表达的转录因子和分泌的细胞因子不同可将ILCs分为ILC1、ILC2、ILC3三种，ILC1和ILC3又包括几个不同的亚型。ILCs对维持肠道黏膜上皮的完整性、调节肠道菌群、促进肠道免疫系统发育和调节肠道炎症反应等具有重要的作用。本文主要就ILCs在维持肠道稳态和在肠道疾病发生发展的作用做一综述。

关键词：固有淋巴细胞肠道菌群炎症性肠病结直肠癌

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生命早期肠道菌群的变迁及相关影响因素研究进展

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中华临床营养杂志 2018年第2期26卷 121-124页

作者：杨蓉秦环龙上海市第十人民医院儿科 200072 上海市第十人民医院普外科 200072 同济大学医学院肠道疾病研究所上海200072

生命早期的肠道菌群主要来源于母体和新生儿之间的菌群交换.从胎儿分娩至儿童期,肠道菌群经历着一个动态的变迁.越来越多研究表明分娩方式、婴儿喂养方式、抗生素的使用是生命早期肠道菌群变迁的主要影响因素,但具体机制仍有待进一步探... 详细信息

生命早期的肠道菌群主要来源于母体和新生儿之间的菌群交换.从胎儿分娩至儿童期,肠道菌群经历着一个动态的变迁.越来越多研究表明分娩方式、婴儿喂养方式、抗生素的使用是生命早期肠道菌群变迁的主要影响因素,但具体机制仍有待进一步探索.本文就生命早期肠道菌群的变迁及相关影响因素进行简要综述.

关键词：生命早期菌群变迁分娩方式喂养方式抗生素使用

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